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Treatment for Minimal/Mild Disease
R.S. Schenken
The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.
The management of patients with minimal/mild endometriosis is controversial. This is due to our
meager understanding of the pathophysiology of endometriosis-related symptoms and the paucity of
randomized treatment trials. In general, treatment is dependent on the patient’s presenting
symptoms. Patients with pelvic pain maybe managed with surgery or medical treatment. Patients
desiring pregnancy are managed surgically or with specific infertility treatments. A special
circumstance exists when minimal/mild endometriosis is diagnosed in an asymptomatic patient.
Treatment of Asymptomatic Women
The prevalence of endometriosis is estimated to be 2-3% and minimal/mild disease is often
encountered in asymptomatic women undergoing surgery for other indication (i.e. sterilization).1
Some recommend treatment of asymptomatic endometriosis to prevent disease progression.2
Evidence suggests that in approximately 30-50% of women, the disease is indeed progressive2,3,4
and this may depend on the type of lesions present.5 While it seems rational to perform
laparoscopic cytoreduction at the time of diagnosis,6 there is no evidence that this approach
prevents recurring of the disease or subsequent symptoms. Medical therapy for asymptomatic
incidental minimal/mild endometriosis is an expensive alternative that has no supporting evidence.
It has yet to be proven that medical therapy greatly influence the natural history of endometriosis.
Treatment of Pelvic Pain
Minimal/mild endometriosis, as defined by the American Society of Reproductive Medicine
classification, may include not only superficial disease, but deeply invasive nodules that are
frequently associated with pain.5 Direct comparison of surgical versus medical therapy in treating
endometriosis associated pain have not been conducted. Available data suggests that surgery is as
efficacious as medical therapy.7 A randomized trial compared laparoscopic laser ablation of
endometriosis to expectant management and reported pain relief in 63% and 23%, respectively, after
6 months.3 Surgical treatment at the time of diagnosis is a practical approach that is associated with
low complication rates.8 The potential exists for adhesion following extirpation, however, de novo
adhesion formation is uncommon with laparoscopic surgery.9 Surgery also avoids the expense and
side effects of medical therapy. Further, there is a high rate of pain recurrence following
discontinuation of medical treatment.10 Some have recommended the use of post-operative medical
therapy to delay the return of symptoms requiring further treatment.11 This approach has not been
shown to be effective specifically in case of minimal/mild disease.
Treatment of Infertility
There is no current evidence that medical treatment of endometriosis in infertile women improves
fecundity. A meta-analysis by Hughes and colleagues included seven studies comparing medical
therapy to no treatment or placebo.12 The common odd ratio for pregnancy following medical
therapy was 0.85 (95% CI, 0.95 to 1.22).
Two prospective, controlled, randomized studies indicate that danazol is no better than expectant
management for infertility associated with minimal endometriosis.13,14 A recent randomized,
controlled trial included 71 women with rAFS stage I or II endometriosis that received the GnRH
agonist analog buserelin (400 ug three times a day for 6 months) or no treatment.14 The 1- and 2year actuarial pregnancy rates were similar in both groups. Hull and associates reported a controlled
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comparative trial with oral medroxyprogesterone, danazol, and expectant management in women
with stage I and II endometriosis.15 Pregnancy rates in the three groups, respectively, were 71%,
46%, and 55%, and there were no significant differences among groups.
Two randomized studies have assessed pregnancy rates following surgical treatment or expectant
management. The Canadian Collaborative Group of Endometriosis reported a randomized trial of
laparoscopy with or without treatment in 341 women with stage I/II disease. The fecundity rate in
treated patients was 4.7 versus 2.4 per 100 person-months in controls (95% CI 1.2 to 3.1).16
However, the Gruppo Italiano per lo Studio dell’ Endometriosi conducted a similar study in 111
patients with stage I/II endometriosis.17 One year after surgery, the pregnancy rate was 29% in the
no treatment group and 24% in the ablation/resection group. These conflicting studies may be due to
different patient populations or responses of individual patients to therapy.
Several studies report success with COH/IUI in the treatment of endometriosis-associated infertility.
In a randomized controlled trial, comparing clomiphene citrate and IUI with preovulatory
intercourse in patients with unexplained infertility and surgically corrected endometriosis.18 A
statistically significant increased in cycle fecundity was seen with four cycles of clomiphene
citrate/IUI compared with controls (0.095 versus 0.033, respectively).
Fedele and colleagues randomized 40 women with stage I/II endometriosis and infertility to receive
either three cycles of HMG-IUI or no treatment (expectant management).14 The cycle fecundity
was 0.15 in the HMG-IUI group and 0.045 in the untreated group (p < 0.05). Kemmann and associates reported on the effects of expectant management, clomiphene citrate, HMG, or IVF/ET on
cycle fecundity in women with infertility and minimal or mild endometriosis.19 The increase in
cycle fecundity with HMG and IVF/ET was statistically significant. Both of these studies suggest
that treatment for women with infertility and minimal or mild endometriosis should involve a
gradual increase in the intensity of empiric therapy (Table 1).
References
1.
CANDIANI GB, VERCELLINI P, FEDELE L, COLOMBO A, CANDIANI M. Mild
endometriosis and infertility: a critical review of epidemiologic data, diagnostic pitfalls, and
classification limits. Obstet Gynecol Surv 1991; 46:374-82.
2.
THOMAS EJ, COOKE ID. Impact of gestrinone on the course of asymptomatic
endometriosis. Br Med J Clin Res Ed. 1987; 294:272-4.
3.
SUTTON CJG, POOLEY AS, EWEN SP, HAINES P. Follow-up report on a randomized
controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal
to moderate endometriosis. Fertil Steril 1997; 68:1070-4.
4.
SCHENKEN RS, GUZICK, DS. Revised endometriosis classification: 1996. Fertil Steril
1997; 67:815-6.
5.
KONINCKS PR, MEULEMAN C, DEMEYERE S, ET AL. Suggestive evidence that pelvic
endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is
associated with pelvic pain. Fertil Steril 1991; 55:759-65.
6.
MURPHY AA, SCHLAFF WD, HASSIAKOS D, ET AL. Laparoscopic cautery in the
treatment of endometriosis-related infertility. Fertil Steril 1991; 55:246-51.
7.
SCHENKEN RS. Endometriosis. In: Scott JR, DiSaia PJ, Hammond CB, Spellacy WN, eds.
Danforth's Obstetrics and Gynecology. Chapter 42, Philadelphia: Lippincott Williams &
Wilkins, 1999:669-75.
8.
WILLIAMS TJ, PRATT JH. Endometriosis in 1,000 consecutive celiotomies: incidence and
management. Am J Obstet Gynecol 1977; 129:245-50.
9.
OPERATIVE LAPAROSCOPY STUDY GROUP. Postoperative adhesion development
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10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
after operative laparoscopy: evaluation at early second-look procedures. Fertil Steril 1991;
55:700-4.
MILLER JD, SHAW RW, CASPER RFJ, ET AL. Historical prospective cohort study of the
recurrence of pain after discontinuation of treatment with danazol or a gonadotropinreleasing hormone agonist. Fertil Steril 1998; 70:293-6.
HORNSTEIN MD, HEMMINGS R, YUZPE AA, HEINRICHS WL. Use of nafarelin versus
placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 1997; 68:860-4.
HUGHES EG, FEDORKOW DM, COLLINS JA. A quantitative overview of controlled
trails in endometriosis-associated infertility. Fertil Steril 1993; 59:963-70.
BAYER SR, SEIBEL MM, SAFFAN DS, ET AL. Efficacy of danazol treatment for
minimal endometriosis in infertile women: a prospective randomized study. J Reprod Med
1988; 33:179-83.
FEDELE L, PARAZZINI F, RADICI E, ET AL. Buserelin acetate versus expectant
management in the treatment of infertility associated with minimal or mild endometriosis: a
randomized clinical trial. Am J Obstet Gynecol 1992; 166:1345-50.
HULL ME, MOGHISSI KS, MAGYAR DF, HAYES MF. Comparison of different
treatment modalities of endometriosis in infertile women. Fertil Steril 1987; 47:40-4.
MARCOUX S, MAHEUX R, BERUBE S, THE CANADIAN COLLABORATIVE
GROUP OF ENDOMETRIOSIS. Laparoscopic surgery in infertile women with minimal or
mild endometriosis. N Engl J Med 1997; 337:217-22.
PARAZZINI, F. Ablation of lesions or no treatment in minimal-mild endometriosis in
infertile women: a randomized trial. Hum Reprod 1999; 14:1332-4.
DEATON JL, GIBSON M, BLACKMER KM, NAKAJIMA ST, BADGER GJ,
BRUMSTED JR. A randomized, controlled trial of clomiphene citrate and intrauterine
insemination in couples with unexplained infertility or surgically corrected endometriosis.
Fertil Steril 1990; 54:1083-8.
KEMMANN E, CHAZI D, CORSAN G, ET AL. Does ovulation stimulation improve
fertility in women with minimal/mild endometriosis after laser laparoscopy? Int J Fertil
Menopausal Stud 1993; 38:16-21.
Table 1. Cycle Fecundity in Women with Stage I/II Endometriosis
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